p38 MAPK Inhibitor (SB203580) and Metformin Reduces Aortic Protein Carbonyl and Inflammation in Non-obese Type 2 Diabetic Rats

Nokkaew, Nuttikarn; Mongkolpathumrat, Podsawee; Junsiri, Ruttanapong; Jindaluang, Supawit; Tualamun, Nichagron; Manphatthanakan, Niya; Saleesee, Nareumon; Intasang, Marisa; Sanit, Jantira; Adulyaritthikul, Punyanuch; Kongpol, Kantapich; Kumphune, Sarawut; Nernpermpisooth, Nitirut

doi:10.1007/s12291-019-0815-9

Cited by 6 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SB203580 inhibits the p38MAPK pathway by competitively binding to the ATP site with p38 MAPK, thus making p38 MAPK lose the ability to bind to ATP. And then SB203580 inhibits the phosphorylation of p38 MAPK, prompting it to lose kinase activity [19]. In addition, HIBI rats were treated with Dehydrocorydaline (DHC) in this study.…”

Section: Discussionmentioning

confidence: 99%

Effects of p38 MAPK signaling pathway on cognitive function and recovery of neuronal function after hypoxic-ischemic brain injury in newborn rats

Zhu

et al. 2020

Journal of Clinical Neuroscience

View full text Add to dashboard Cite

To explore the effects of p38 MAPK signaling pathway on cognitive function and recovery of neuronal function after hypoxic-ischemic brain injury (HIBI) in newborn rats. Seventy-two healthy SPF grade SD newborn rats were randomly and equally divided into Normal group (healthy rats) and Sham group (rats underwent sham operation), Model group (HIBI model rats), p38 MAPK Inhibitor group (HIBI model rats treated with p38 MAPK inhibitor) and p38 MAPK Activator group (HIBI model rats treated with p38 MAPK activator). On postnatal day 28, Morris water maze, tail suspension test and inclined plane test were conducted on rats in each group. Twenty-four hours after modeling, the expression of p-p38 MAPK protein and apoptosis related genes in rat hippocampal tissues was detected by TUNEL staining, qRT-PCR and Western blot. Compared with Normal group, escape latency and inclined plane test time were prolonged, the number of passing through the platform and tail suspension time were reduced (all P < 0.05); Bax and Caspase-3 mRNA and protein expression levels and p-p38 MAPK protein level were increased, Bcl-2 mRNA level was decreased, and neuronal apoptosis proportion was increased in Model group (all P < 0.05). Compared with Model group, the above indicators showed reversed and enhanced trends in p38 MAPK Inhibitor and p38 MAPK Activator groups, respectively (all P < 0.05). Inhibition of p38 MAPK signaling pathway can effectively improve the learning and memory ability and motor function of newborn rats with HIBI, and reduce neuronal apoptosis in the hippocampal tissues, thereby promoting neuronal recovery.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of p38 MAPK signaling pathway on cognitive function and recovery of neuronal function after hypoxic-ischemic brain injury in newborn rats

Zhu

et al. 2020

Journal of Clinical Neuroscience

View full text Add to dashboard Cite

show abstract

“…Specifically, NF‐κB plays a central role in the interplay between various pathological mechanisms of DKD, such as the activation of the renin‐angiotensin system, accumulation of advanced glycation end products (AGEs), and oxidative stress 49 . In renal innate cells (including mesangial cells, podocytes, endothelial cells, and tubular epithelial cells), NF‐κB can be rapidly activated by various stimuli, such as hyperglycemia, mechanical stress, angiotensin II, and proteinuria, and activated NF‐κB can activate the expression of some inflammatory genes through oxidative stress, AGEs, protein kinase C, and MAPK 50,51 . NF‐κB p65 is upregulated in the kidneys of animal models of diabetes and can induce renal injury by activating various signaling pathways in glomerular and tubular cells 52,53 .…”

Section: Discussionmentioning

confidence: 99%

“…including mesangial cells, podocytes, endothelial cells, and tubular epithelial cells), NF-κB can be rapidly activated by various stimuli, such as hyperglycemia, mechanical stress, angiotensin II, and proteinuria, and activated NF-κB can activate the expression of some inflammatory genes through oxidative stress, AGEs, protein kinase C, and MAPK 50,51. NF-κB p65 is upregulated in the kidneys of animal models of diabetes and can induce renal injury by activating various signaling pathways in glomerular and tubular cells 52,53.…”

mentioning

confidence: 99%

Qi‐dan‐dihuang decoction ameliorates renal fibrosis in diabetic rats via p38MAPK/AKT/mTOR signaling pathway

Kuang,

You,

et al. 2024

Environmental Toxicology

View full text Add to dashboard Cite

ContextQi‐dan‐dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood.ObjectiveThis study reveals the mechanism by which QDD ameliorates DKD.Materials and MethodsThe compounds in QDD were identified by high‐performance liquid chromatography and quadrupole‐time‐of‐flight tandem mass spectrometry (HPLC‐Q‐TOF‐MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD‐low (QDD‐L), and 2% QDD‐high (QDD‐H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose‐treated HK‐2 and NRK‐52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated.ResultsA total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) and mitogen‐activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial‐mesenchymal transition (EMT) via the p38MAPK and AKT‐mammalian target of rapamycin (mTOR) pathways.Discussion and ConclusionQDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD.

show abstract

“…In vivo studies, renal brosis can be improved by blocking MAPK signaling pathway [41]. In vitro studies shown that, under high glucose, p38MAPK activation promotes renal tubular epithelial cell EMT progress [42], and p38 inhibitor SB203580 signi cantly reverses the EMT progress by downregulated the expression of E-Cadherin and type 1 collagen in HK-2 cells [43,44]. mTOR is a serine/threonine kinase, which belongs to the family of phosphatidylinositol kinase-related kinases.…”

Section: Discussionmentioning

confidence: 99%

Protective Mechanism of Qi-Dan-Dihuang Decoction in Diabetic Kidney Disease Based on Network pharmacology

Kuang¹,

You²,

Qi³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Qi-Dan-Dihuang Decoction (QDD) has been used for treating diabetic kidney disease (DKD), but the mechanisms are poorly understood. The aim of this study is to reveal the therapeutic effects and the mechanism of QDD in ameliorating DKD by network pharmacology, in vivo, and in vitro studies.Methods: The effect of QDD on body weight, fast blood glucose, oral glucose tolerance test (OGTT), 24 h urinary protein (24hU-Pro), serum creatinine (Scr), blood urea nitrogen (BUN), and pathological evaluation in kidney were investigated in vivo using C57BLKS/J db/db mice. The main active compounds of QDD, compound-disease interaction targets, and related processes and pathways were discerned by network pharmacology analysis through Chinese Medicine Systems Pharmacology Database (TCMSP) and TCM Database@Taiwan. The protein-protein interaction (PPI) network were established through STRING database. GO and KEGG pathway were used for analysis processes and pathways. Then Western blot was used to verified the predicted results. Finally, cell viability, wound healing and mainly pathway protein expression were detected in vitro using renal tubular epithelial cells HK-2 and NRK-52E cells.Results: Although QDD treatment showed no significant difference in FBG and AUC of OGTT, but had significant reduction in Scr level in C57BLKS/J db/db mice. Histopathologic results showed that QDD ameliorated the expansion of mesangial area, thickened membranes of Bowman’s capsules and basement membrane of glomerular capillaries, renal tubular epithelial cells vacuolar degeneration and reversed the glomerular and tubulointerstitial in C57BLKS/J db/db mice. For network pharmacology analysis of QDD, 143 active compounds related to 274 possible targets in QDD obtained and 117 compound-disease interaction targets were screened out combining with Genecards database. 18 key targets was excavated through network topological analysis. GO and KEGG pathway enrichment analysis showed that compound-disease interaction targets were significantly enriched in processes and pathways that are closely related to DKD. Western blot results showed that QDD significantly attenuated EMT-related proteins, p-NF-κb, IL-1β, IL-18, p-p38MAPK/p38MAPK, p-AKT/AKT, and p-mTOR/ mTOR protein expressions. Treatment with QDD could alleviate cell viability damaged, EMT process, p-NF-κb, IL-1β, IL-18, p-p38MAPK/p38MAPK, p-AKT/AKT and p-mTOR/ mTOR protein expressions by high D-gulcose.Conclusions: This study provides convincing evidence suggest that QDD protects renal fibrosis of DKD, by regulating EMT in RTECs and inflammatory response through p38MAPK and AKT/mTOR signaling pathways.

show abstract

p38 MAPK Inhibitor (SB203580) and Metformin Reduces Aortic Protein Carbonyl and Inflammation in Non-obese Type 2 Diabetic Rats

Cited by 6 publications

References 19 publications

Effects of p38 MAPK signaling pathway on cognitive function and recovery of neuronal function after hypoxic-ischemic brain injury in newborn rats

Effects of p38 MAPK signaling pathway on cognitive function and recovery of neuronal function after hypoxic-ischemic brain injury in newborn rats

Qi‐dan‐dihuang decoction ameliorates renal fibrosis in diabetic rats via p38MAPK/AKT/mTOR signaling pathway

Protective Mechanism of Qi-Dan-Dihuang Decoction in Diabetic Kidney Disease Based on Network pharmacology

Contact Info

Product

Resources

About